**7. Application of external pressures to eradicate biofilm**

Several biochemical and physical methods can be used to eradicate formed biofilms as described in **Figure 5.**


*Bacterial Biofilm Eradication in Human Infections DOI: http://dx.doi.org/10.5772/intechopen.113341*

> microorganisms (**Figure 5B**). At a later stage of infection, bacteriophages express peptidoglycan hydrolases known as phage lysins. They have the ability to destroy bacteria by cleaving the peptidoglycan layer of the cell wall (**Figure 5B**) [35].


#### **Figure 5.**

*Application of external pressures to eradicate mature biofilm, which include (A) ultrasound, (B) phage lysins, (C) degradative enzymes, and (D) microbial metabolites [26].*

e.Nitric oxide: At low and non-toxic concentrations, NO produced by the anaerobic respiration activities inside the *P. aeruginosa* biofilm can start the dispersal of the biofilm. Further investigation indicated that *P. aeruginosa* biofilm NO signaling can increase PDE activity, lowering intracellular c-di-GMP levels and promoting biofilm dispersion. NO-induced biofilm dispersal was also seen in several other bacteria, including *E. coli* and *S. aureus*, in addition to *P. aeruginosa*. Similarly, exogenous NO addition therapy can promote biofilm dispersion. For instance, NO-releasing polymers have the ability to dose-dependently lower the metabolic activity of different biofilms. Additionally, regardless of the matrix's composition, NO-releasing cyclodextrins can destroy *P. aeruginosa* biofilm. A supramolecular nanocarrier was created by combining the NO prodrug with the glutathione-sensitive a-cyclodextrin and chlorin e6 prodrug demonstrate quick NO release when glutathione is overexpressed in the biofilm, effectively destroying the *S. aureus* biofilm [37].
